As a result of a National Cancer Institute-sponsored initiative to discover novel anti-HIV agents from natural sources, the alkaloid michellamine B was identified in 1991. Michellamine B shows broad anti- HIV activity against HIV-1 and HIV-2 as well as some resistant strains of the virus. Although its isolation was only reported in December, 1991, michellamine B is now in advanced preclinical development (he so- called DNIIA stage). Michellamine B was isolated from a vine that grows in Cameroon. Substantial quantities are required for its continued evaluation and development. This project has two main objectives. The first is the development of a short (ca. ten steps from readily available starting materials), practical synthesis capable of furnishing michellamine B in substantial quantities (initially tens of grams, ultimately considerably more). The second major objective is to use that synthesis to prepare analogs both for structure activity relationship (SAR) studies, but also with the goal of producing analogs with better efficacy and/or potency than michellamine B.